Localized thermotherapy is used in a growing number of institutions around the world to treat solid malignant tumors. The therapy consists of heating the tumors to temperatures several degrees centigrade above core temperature (hyperthermic temperatures) and maintaining the tumors at hyperthermic temperatures for a preset period. This procedure is usually repeated several times. Thermotherapy is given either alone or in combination with ionizing radiation or chemotherapy. Clinical results with a variety of malignancies have been encouraging, as described in, for example, Prog. Exp. Tumor Res. 28:198-219, 1984.
Malignant brain tumors are candidates for localized thermotherapy. Such tumors do not metastasize, so that only local control is required. Also, when conventional techniques such as surgery, radiotherapy, or chemotherapy are used to treat malignant brain tumors, the prognosis is usually discouraging. Attempts to treat human brain cancers with thermotherapy date back to 1971, when Sutton in Trans. Am Neurol Assoc. 96:195-199, 1971, reported encouraging results using a combination of thermotherapy induced with an invasive resistive heater and chemotherapy. There was little follow-up to Sutton's work until 1981, when Salcman and Samaras published an article on the biophysical rationale for treating malignant brain tumors with thermotherapy using invasive microwave antennas in Neurosurgery 9:327-335, 1981. Since 1981, a few centers have begun to treat a small number of patients who have malignant brain tumors with localized thermotherapy. (See Prog. Exp. Tumor Res. 28:220-231, 1984.)
The rationale for using microwave-localized thermotherapy for treating malignant brain tumors can be summarized as follows:
1. By using small, invasive applicators, it is possible to guide microwave energy directly into the interior of the malignant brain tumor (see J. Microwave Power 14:339-350, 1979.) Most of the microwave energy broadcast by the antennas of these applicators is absorbed by the tumor tissues, and only a small fraction of the microwave energy usually reaches the healthy tissues surrounding the tumors. The malignant tissues are therefore preferentially heated to higher temperatures than the healthy tissues. Thus, it becomes possble to damage or destroy malignant tissues by heating them to hyperthermic temperatures, while sparing healthy tissues. This preferential damage or destruction of malignant cells by microwave heating is often amplified because malignant cells are often more senstive to insult by heat than are healthy cells. This is because malignant cells, particularly those in the interior of tumors, are often in a state of nutritional deprivation, low pH, and chronic hypoxia (Cancer Res (suppl) 44:4703-4908, 1984). Furthermore, the microvasculature of tumors, being not as well developed and resistant to insult as healthy microvasculature, is more easily damaged by heat than healthy microvasculature (Radiology 137:515-521, 1980). Cells fed by microvasculatures that have been damaged by heat become in turn weakened and more sensitive to heat.
2. Localized thermotherapy enhances the effectiveness of radiotherapy and chemotherapy (Prog. Exp. Tumor Res. 28:198-219, 1984) because (a) thermotherapy interferes with the repair of cells that have been sublethally damaged by radiation; (b) cells in the S phase of the cell cycle which are resistant to ionizing radiation, are very heat-sensitive; (c) hypoxic tumor cells, which tend to be resistant to ionizing radiation and chemotherapy, are especially sensitive to thermotherapy; (d) thermotherapy is effective in oxygenating radioresistant hypoxic cells; and (e) thermotherapy magnifies the cytoxicity of many anticancer drugs.
3. There is evidence that localized thermotherapy stimulates immunological responses (J. Microwave Power 11:168-170, 1976) by causing infiltration of heated tumor sites by macrophages and T lymphocytes (Cancer 43:767-783, 1979). This immunological response can be effective in inhibiting renewed brain tumor growth at the periphery of heated tumors.